title: Regulation of glycogen synthase kinase 3beta functions by modification of the small ubiquitin-like modifier.
abstract: Modification of the Small Ubiquitin-like Modifier (SUMO) (SUMOylation) appears to regulate diverse cellular processes, including nuclear transport, signal transduction, apoptosis, autophagy, cell cycle control, ubiquitin-dependent degradation and gene transcription. Glycogen synthase kinase 3beta (GSK 3beta) is a serine/threonine kinase that is thought to contribute to a variety of biological events, including embryonic development, metabolism, tumorigenesis, and cell death. GSK 3beta is a constitutively active kinase that regulates many intracellular signaling pathways by phosphorylating substrates such as beta-catenin. We noticed that the putative SUMOylation sites are localized on K(292 )residueof (291)FKFPQ(295) in GSK 3beta based on analysis of the SUMOylation consensus sequence. In this report, we showed that the SUMOylation of GSK 3beta occurs on its K(292) residue, and this modification promotes its nuclear localization in COS-1. Additionally, our data showed that the GSK 3beta SUMO mutant (K292R) decreased its kinase activity and protein stability, affecting cell death. Therefore, our observations at first time suggested that SUMOylation on the K(292) residue of GSK 3beta might be a GSK 3beta regulation mechanism for its kinase activation, subcellular localization, protein stability, and cell apoptosis.
authors.affiliation: School of Science Education, Chungbuk National University, Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea.
authors.forename: Lee
authors.initials: L
authors.lastname: Eun Jeoung
authors.forename: Hyun
authors.initials: H
authors.lastname: Sung Hee
authors.forename: Chun
authors.initials: C
authors.lastname: Jaesun
authors.forename: Shin
authors.initials: S
authors.lastname: Sung Hwa
authors.forename: Yeon
authors.initials: Y
authors.lastname: Kwang Hum
authors.forename: Kwak
authors.initials: K
authors.lastname: Min Kyoung
authors.forename: Park
authors.initials: P
authors.lastname: Tae Yoon
authors.forename: Kang
authors.initials: K
authors.lastname: Sang Sun